title: Making autophagosomes: localized synthesis of phosphatidylinositol 3-phosphate holds the clue.
abstract: Autophagy presents a topological challenge for the cell because it requires delivery of cytosolic material to the lumen of a membrane-bound compartment, the lysosome. This is solved in an ingenious way by the formation of a double-membrane vesicle, the autophagosome, which captures cytosolic proteins and organelles during its transformation from a planar membrane disk into a sphere. In this way, cytosolic material first becomes lumenal and is then delivered for degradation to the lysosome. An unsolved set of questions in autophagy concerns the membrane of the autophagosome: what are the signals for its formation and what is its identity? Recently we provided some clues that may help answer these questions. By following the dynamics of several phosphatidylinositol 3-phosphate (PI3P)-binding proteins during amino acid starvation (and autophagy induction) we concluded that at least some autophagosomes are formed in a starvation-induced, PI3P-enriched membrane compartment dynamically connected to the endoplasmic reticulum (ER). We termed the membranes of this compartment omegasomes (from their omega-like shape). Our data suggest that PI3P is important for providing localization clues and perhaps for facilitating the fusion step at the final stage of autophagosome formation.
authors.affiliation: Signalling Programme, Babraham Institute, Babraham, Cambridge, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Walker
authors.forename: Priya
authors.initials: P
authors.lastname: Chandra
authors.forename: Maria
authors.initials: M
authors.lastname: Manifava
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Axe
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ktistakis
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D010588:Phagosomes / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism
chemical_list: D000596:Amino Acids; D018129:Phosphatidylinositol Phosphates; D011506:Proteins; C055525:phosphatidylinositol 3-phosphate